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1.
Carbohydr Polym ; 193: 173-178, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29773369

RESUMO

Magnetite-nanoparticle-containing red-blood-cell-like-microparticles (M-RBC-MPs) with a selective ability for trapping cortisol (COR) were synthesized by an electrospray technique of a molecularly imprinted ethyl(hydroxyethyl) cellulose (EHEC)-based precursor. The as-synthezied M-RBC-MPs were ∼3-µm-disks with a dent. M-RBC-MPs contained magnetite nanoparticles below 15 nm in diameter, which exhibited magnetization and no room-temperature coercivity. The molecularly imprinted M-RBC-MPs (MI-M-RBC-MPs) passed through pores less than their diameter. The MI-M-RBC-MPs selectively trapped COR from a solution containing molecules similar to COR, whereas non-imprinted M-RBC-MPs did not trap COR. Furthermore, magnets were used to capture the water-dispersed MI-M-RBC-MPs flowing in a tube. Based on the above results, MI-M-RBC-MPs may selectively trap COR while simultaneously circulating in the blood, followed by their removal from the blood using magnets.


Assuntos
Micropartículas Derivadas de Células/química , Celulose/química , Eritrócitos/química , Hidrocortisona/isolamento & purificação , Nanopartículas de Magnetita/química , Impressão Molecular , Humanos , Hidrocortisona/química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
2.
ACS Biomater Sci Eng ; 4(8): 2729-2732, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-33434998

RESUMO

Prolonging the circulation time (CT) of microparticles (MPs) in the blood is key for a successful microparticle-based medicinal approach to serve as drug delivery systems (DDSs). Previously, we reported that MPs that mimic the shape of red blood cells (RBCs) avoid accumulation in the spleen and lungs. We now describe the effectiveness of mimicking not only the shape of RBCs but also their surface structure for the prolongation of CT. RBC-shaped MPs (RBC-MPs) were electrosprayed with cellulose and covered with a native RBC membrane (RBCM) collected from mouse blood. Seven hours after intravenous injection, approximately twice as many RBCM-covered RBC-MPs (RBC-MPs@RBCM) were present in the blood of mice compared to unmodified RBC-MPs. Twenty-four hours postinjection, the concentration of RBC-MPs@RBCM in the blood was 4 times higher. These findings suggest that an RBCM covering the MPs contributed to significant CT prolongation, which may positively impact their applications as DDSs.

3.
Biomaterials ; 156: 45-55, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29190497

RESUMO

Micro-sized drug-carrier particles accumulate mainly in the lungs and nano-sized particles tend to accumulate in the liver and spleen. Here, we show that micro-particles designed to mimic red blood cells (RBCs) can overcome these limitations. The RBC-MPs created in this study have a unique intra-particle elasticity distribution (IED), enabling them to bend around the central axis of the RBC-like dent, enabling them to pass through pores smaller than their diameter, mechanically behaving as authentic RBCs. In contrast, spherical MPs (SPH-MPs) and RBC-MPs hardened by incorporating a siloxane network (SiO2-RBC-MPs), could not. In addition to the IED, we discovered that the deformability also depends on the shape and average particle elasticity. RBC-MPs did not accumulate in the lungs and the spleen, but were targeted specifically to the liver instead. In contrast, non-RBC-MPs such as SPH-MPs and SiO2-RBC-MPs showed heavy accumulation in the lungs and/or spleen, and were dispersed non-specifically in various organs. Thus, controlling the shape and mechanical properties of RBC-MPs is important for achieving the desired biodistribution. When RBC-MPs were loaded with a (TGF)-ß receptor inhibitor, RBC-MPs could treat liver fibrosis without pneumotoxicity.


Assuntos
Eritrócitos/metabolismo , Cirrose Hepática/terapia , Pulmão/metabolismo , Microesferas , Baço/metabolismo , Animais , Elasticidade , Feminino , Fluorescência , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Porosidade , Distribuição Tecidual
4.
Sci Rep ; 7(1): 3953, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28638087

RESUMO

Multimodal imaging using novel multifunctional nanoparticles provides new approach to biomedical field. Thiol-organosilica nanoparticles containing iron oxide magnetic nanoparticles (MNPs) and rhodamine B (thiol OS-MNP/Rho) were applied to multimodal imaging of hepatic tumor of Long-Evans Cinnamon (LEC) rat. The magnetic resonance imaging (MRI) of LEC rats revealed tumors in the liver clearly and semi-quantitatively due to a labeling of macrophages in liver. The fluorescent imaging (FI) showed abnormal fluorescent patterns of the liver at the mesoscopic level that was between macroscopic and microscopic level. We performed correlation analysis between optical imaging including FI and MRI. We found that the labeled macrophages located specific area in the tumor tissue and influenced the tumor size on MRI. In addition histological observation showed the labeled macrophages related specific tissue in the pathological region. We demonstrated a new approach to evaluate tumor tissue at the macroscopic and microscopic level as well as mesoscopic level using multimodal imaging.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita , Imagem Multimodal/métodos , Animais , Compostos Férricos/química , Processamento de Imagem Assistida por Computador , Macrófagos/patologia , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Nanotecnologia , Imagem Óptica/métodos , Ratos Endogâmicos LEC , Rodaminas/química
5.
J Colloid Interface Sci ; 492: 127-135, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28086116

RESUMO

Multimodal imaging using novel multifunctional nanoparticles provides a new approach for the biomedical field. Thiol-organosilica nanoparticles containing iron oxide magnetic nanoparticles (MNPs) as the core and rhodamine B in the thiol-organosilica layer (thiol OS-MNP/Rho) were synthesized in a one-pot process. The thiol OS-MNP/Rho showed enhanced magnetic resonance imaging (MRI) contrast and high fluorescence intensity. The relaxometry of thiol OS-MNP/Rho revealed a novel coating effect of the organosilica layer to the MNPs. The organosilica layer shortened the T2 relaxation time but not the T1 relaxation time of the MNPs. We injected thiol-OS-MNP/Rho into normal mice intravenously. Injected mice revealed an alteration of the liver contrast in the MRI and a fluorescent pattern based on the liver histological structure at the level between macroscopic and microscopic fluorescent imaging (mesoscopic FI). In addition, the labeled macrophages were observed at the single cell level histologically. We demonstrated a new approach to evaluate the liver at the macroscopic, microscopic level as well as the mesoscopic level using multimodal imaging.


Assuntos
Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Nanopartículas/química , Imagem Óptica/métodos , Compostos de Organossilício , Animais , Compostos Férricos/química , Corantes Fluorescentes/química , Magnetismo , Nanopartículas de Magnetita/química , Camundongos , Microscopia de Fluorescência , Compostos de Organossilício/química
6.
ACS Biomater Sci Eng ; 3(6): 1129-1135, 2017 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-33429587

RESUMO

Techniques to elucidate the kinetics and distribution of the same cells in the whole body and in tissues are necessary for further studies of cancer, immunity, and regenerative medicine. Fluorescent imaging is a powerful technique for visualization of cells. However, current fluorescent probes are applicable in either the ultraviolet (UV)-visible (Vis) region (300-650 nm) or the biological transparency window (BTW, 650-900 nm), but not both. Thus, they cannot serve as fluorescent probes for both in vivo and in vitro imaging, and it is difficult to achieve imaging of the same cells seamlessly from the cellular level to the whole body and tissue levels using currently available fluorescent probes. Accordingly, in this paper, we describe organic-inorganic hybrid nanoparticles (HNPs) that could be used to achieve seamless tracking of the same cells. Within the HNPs, a porphyrin molecule, Vis-fluorophore, was surrounded by a siloxane chain, preventing the aggregation of porphyrin molecules. As a result, the porphyrin fluorescence was not quenched. Furthermore, indocyanine green (ICG), a BTW fluorophore, was localized on the HNP surface, leading to fluorescence resonance energy transfer (FRET) from porphyrin to ICG only near the HNP surface. Through the above structural design, the HNPs acquired both excitation (λex) and emission (λem) wavelengths in the visible region and BTW, respectively, as well as large Stokes shifts. The HNP-labeled immune cells successfully and the labeled cells were separated easily from unlabeled cells by fluorescence-activated cell sorting. The kinetics of the labeled cells in the whole body were revealed by fluorescence imaging within BTW. Furthermore, the distributions of the same labeled cells were elucidated by histological analysis within the UV-vis region. Thus, the HNPs served as fluorescent probes for seamless tracking of the same cells.

7.
ACS Biomater Sci Eng ; 3(1): 95-105, 2017 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33429683

RESUMO

Magnetic-resonance-imaging (MRI)-guided magnetic thermochemotherapy is a potentially invasive technique combining diagnosis and treatment. It requires the development of multifunctional nanoparticles with (1) biocompatibility, (2) high relaxivity, (3) high heat-generation power, (4) controlled drug release, and (5) tumor targeting. Here, we show the synthesis of such multifunctional nanoparticles ("Core-Shells") and the feasibility of MRI-guided magnetic thermochemotherapy using the synthesized nanoparticles. "Tight" iron-oxide nanoparticle clustering to zero interparticle distance within the Core-Shells boosts the relaxivity and heat-generation power while maintaining biocompatibility. The initial Core-Shell drug release occurs in response to an alternating magnetic field (AMF) and continues gradually after removal of the AMF. Thus, a single Core-Shell dose realizes continuous chemotherapy over a period of days or weeks. The Core-Shells accumulate in abdomen tumors, facilitating MRI visualization. Subsequent AMF application induces heat generation and drug release within the tumors, inhibiting their growth. Core-Shell magnetic thermochemotherapy exhibits significantly higher therapeutic efficacy than both magnetic hyperthermia and chemotherapy alone. More importantly, there are minimal side effects. The findings of this study introduce new perspectives regarding the development of materials for MRI, magnetic hyperthermia, and drug delivery systems. Both conventional and novel iron-oxide-based materials may render theranostics (i.e., techniques fusing diagnosis and treatment) feasible.

8.
Theranostics ; 4(8): 834-44, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24955144

RESUMO

We report the synthesis of smart nanoparticles (NPs) that generate heat in response to an alternating current magnetic field (ACMF) and that sequentially release an anticancer drug (doxorubicin, DOX). We further study the in vivo therapeutic efficacy of the combination of magnetic hyperthermia (MHT) and chemotherapy using the smart NPs for the treatment of multiple myeloma. The smart NPs are composed of a polymer with a glass-transition temperature (T g) of 44°C, which contains clustered Fe3O4 NPs and DOX. The clustered Fe3O4 NPs produce heat when the ACMF is applied and rise above 44°C, which softens the polymer phase and leads to the release of DOX. The combination of MHT and chemotherapy using the smart NPs destroys cancer cells in the entire tumor and achieves a complete cure in one treatment without the recurrence of malignancy. Furthermore, the smart NPs have no significant toxicity.


Assuntos
Liberação Controlada de Fármacos , Hipertermia Induzida , Fenômenos Magnéticos , Nanopartículas/uso terapêutico , Neoplasias/terapia , Telemedicina/métodos , Animais , Peso Corporal , Feminino , Camundongos , Tamanho do Órgão
9.
Chemistry ; 19(40): 13554-60, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-23939993

RESUMO

The molecular crystals [Li{N(SO2CF3)2}{C6H4(OCH3)2}2] and [Li{N(SO2CF3)2}{C6F2H2(OCH3)2}2] with solid-state lithium ion conductivity have been synthesized by the addition of two equivalents of 1,2-dimethoxybenzene or 1,2-difluoro-4,5-dimethoxybenzene to Li{N(SO2CF3)2}, respectively. Single-crystal X-ray diffraction analysis revealed the formation of ionic conduction paths with an ordered arrangement of lithium ions in these crystal structures, afforded by the self- assembled stacking of molecular-based channels consisting of N(SO2CF3)2 anion and 1,2-dimethoxybenzene frameworks as a result of intermolecular aromatic and hydrogen interactions. These compounds show selective lithium ion conductivity as the anions behave as a component unit of the conduction paths. The relationship between the crystal structure and ionic conductivity of the molecular crystals provides a clue to the development of novel solid electrolytes based on molecular crystals showing fast and selective lithium ion conduction.

10.
Theranostics ; 3(6): 366-76, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23781284

RESUMO

Superparamagnetic nanoparticles (SPIONs) could enable cancer theranostics if magnetic resonance imaging (MRI) and magnetic hyperthermia treatment (MHT) were combined. However, the particle size of SPIONs is smaller than the pores of fenestrated capillaries in normal tissues because superparamagnetism is expressed only at a particle size <10 nm. Therefore, SPIONs leak from the capillaries of normal tissues, resulting in low accumulation in tumors. Furthermore, MHT studies have been conducted in an impractical way: direct injection of magnetic materials into tumor and application of hazardous alternating current (AC) magnetic fields. To accomplish effective enhancement of MRI contrast agents in tumors and inhibition of tumor growth by MHT with intravenous injection and a safe AC magnetic field, we clustered SPIONs not only to prevent their leakage from fenestrated capillaries in normal tissues, but also for increasing their relaxivity and the specific absorption rate. We modified the clusters with folic acid (FA) and polyethylene glycol (PEG) to promote their accumulation in tumors. SPION clustering and cluster modification with FA and PEG were achieved simultaneously via the thiol-ene click reaction. Twenty-four hours after intravenous injection of FA- and PEG-modified SPION nanoclusters (FA-PEG-SPION NCs), they accumulated locally in cancer (not necrotic) tissues within the tumor and enhanced the MRI contrast. Furthermore, 24 h after intravenous injection of the NCs, the mice were placed in an AC magnetic field with H = 8 kA/m and f = 230 kHz (Hf = 1.8×10(9) A/m∙s) for 20 min. The tumors of the mice underwent local heating by application of an AC magnetic field. The temperature of the tumor was higher than the surrounding tissues by ≈6°C at 20 min after treatment. Thirty-five days after treatment, the tumor volume of treated mice was one-tenth that of the control mice. Furthermore, the treated mice were alive after 12 weeks; control mice died up to 8 weeks after treatment.


Assuntos
Hipertermia Induzida/métodos , Imageamento por Ressonância Magnética/métodos , Nanopartículas/administração & dosagem , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Administração Intravenosa , Animais , Modelos Animais de Doenças , Camundongos , Nanomedicina/métodos , Resultado do Tratamento
11.
Chemistry ; 18(48): 15305-9, 2012 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-23129395

RESUMO

A novel trilithium compound, Li(3)[B(C(6)H(4)O(2)){O(CH(2)CH(2)O)(3)CH(3)}(2)][N(SO(2)CF(3))(2)](2) (1-2.0), with solid-state ionic conductivity was synthesized. The crystal structure of 1-2.0 consists of the one-dimensional ionic conduction paths. The paths were afforded as a result of the self-assembled stacking of the component molecules of 1-2.0 with channel structures containing lithium ions. In this supramolecule, one lithium ion holds the component molecules in specific positions to construct a supramolecular structure with thermally stable ionic conduction paths and the others behave as carrier ions exhibiting selective lithium-ion conductivity. Owing to the existence of both roles for the lithium ions, this electrolyte shows selective lithium-ion conductivity.

12.
Inorg Chem ; 51(8): 4689-93, 2012 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-22452625

RESUMO

A novel chiral coordination polymer, [Cu(C(6)H(5)CH(OH)COO)(µ-C(6)H(5)CH(OH)COO)] (1-L and 1-D), was synthesized through a reaction of copper acetate with L-mandelic acid at room temperature. Although previously reported copper mandelate prepared by hydrothermal reaction was a centrosymmetric coordination polymer because of the racemization of mandelic acid, the current coordination polymer shows noncentrosymmetry and a completely different structure from that previously reported. The X-ray crystallography for 1-L revealed that the copper center of the compound showed a highly distorted octahedral structure bridged by a chiral mandelate ligand in the unusual coordination mode to construct a one-dimensional (1D) zigzag chain structure. These 1D chains interdigitated each other to give a layered structure as a result of the formation of multiple aromatic interactions and hydrogen bonds between hydroxyl and carboxylate moieties at mandelate ligands. The coordination polymer 1-L belongs to the noncentrosymmetric space group of C2 to show piezoelectric properties and second harmonic generation (SHG) activity.

13.
Chem Commun (Camb) ; 47(22): 6311-3, 2011 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-21512702

RESUMO

Plastic crystallinity of lithium salt, [LiB(OCH(2)CH(2)OCH(3))(4)] (1), and its solid-state ionic conductivity are disclosed. The addition of small amounts of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) to borate 1 led to the drastic increase of the ionic conductivity and lithium transport number of the electrolyte.

14.
Small ; 6(21): 2384-91, 2010 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-20878793

RESUMO

Red blood cells (RBCs) are able to avoid filtration in the spleen to prolong their half-time in the body because of their flexibility and unique shape, or a concave disk with diameter of some 10 µm. In addition, they can flow through capillary blood vessels, which are smaller than the diameter of RBCs, by morphing into a parachute-like shape. In this study, flexible RBC-like polymer particles are synthesized by electrospraying based on electrospinning. Furthermore, magnetite nanoparticles and fluorescent dye are encapsulated in the particles via in situ hydrolysis of an iron-organic compound in the presence of celluloses. The superparamagnetic behavior of the particles is confirmed by low-temperature magnetic measurements. The particles exhibited not only a dark contrast in magnetic resonance imaging (MRI), but also effective fluorescence. The RBC-like particles with flexibility are demonstrated to have a dual-modality for MRI and fluorescence imaging.


Assuntos
Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Microscopia de Fluorescência/métodos , Animais , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Meios de Contraste/química , Eritrócitos , Camundongos , Microscopia Eletrônica de Varredura , Nanotecnologia
16.
ACS Appl Mater Interfaces ; 2(7): 1903-11, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20568697

RESUMO

Magnetic nanoparticles (MNPs) generate heat when a high-frequency magnetic field (HFMF) is applied to them. Induction heat is useful not only for hyperthermia treatment but also as a driving force for drug-release. beta-Cyclodextrin (CD) can act as drug container because of its inclusion properties. Drugs incorporated in the CD can thus be released through the use of induction heating, or hyperthermic effects, by applying a HFMF. In this study, we have synthesized folic acid (FA) and CD-functionalized superparamagnetic iron oxide nanoparticles, FA-CD-SPIONs, by chemically modifying SPIONs derived from iron(III) allylacetylacetonate. FA is well-known as a targeting ligand for breast cancer tumor and endows the SPIONs with cancer-targeting capability. Immobilization of FA and CD on spinel iron oxide nanoparticles was confirmed by Fourier transform IR (FTIR) and X-ray photoelectron spectroscopy (XPS). The FA-CD-SPIONs have a hydrodynamic diameter of 12.4 nm and prolonged stability in water. They are superparamagnetic with a magnetization of 51 emu g(-1) at 16 kOe. They generate heat when an alternating current (AC) magnetic field is applied to them and have a specific absorption rate (SAR) of 132 W g(-1) at 230 kHz and 100 Oe. Induction heating triggers drug release from the CD cavity on the particle - a behavior that is controlled by switching the HFMF on and off. The FA-CD-SPIONs are noncytotoxic for cells. Thus, FA-CD-SPIONs can serve as a novel device for performing drug delivery and hyperthermia simultaneously.


Assuntos
Portadores de Fármacos , Compostos Férricos/química , Ácido Fólico , Hematínicos , Temperatura Alta , Magnetismo , Nanopartículas/química , Animais , Linhagem Celular , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacologia , Hematínicos/química , Hematínicos/farmacologia , Humanos , Camundongos , Microglia/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
17.
Inorg Chem ; 48(17): 8544-9, 2009 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-19715375

RESUMO

A layered zinc compound is afforded by the heating of zinc acetate dihydrate with mandelic acid in dibenzyl ether. Thermolysis of the layered compound results in the formation of hollow spheres constructed from plate-like ZnO nanocrystals (NCs) in high yield. Size-controlled hollow spheres with a 690 nm diameter (size variation = 6.0%) are obtained by thermal treatment at 300 degrees C for 15 h. In this reaction, the mandelate moiety plays important roles not only in morphology control of ZnO NCs but also for the formation of hollow structures constituted of ZnO nanoplates.

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